Rheumatology in the ICU
Eduardo Santiago M.D
05/16/2012
Airways Problems in
Rheumatologic
Disorders
Synovial joints: CA and CT
Laryngeal Involvement in RA
• Cricoarytenoid joint arthritis.
• Long standing RA but also in newly diagnosed
patients.
• Prevalence: 40%-88%.
• Acute or chronic process with slow
progression of airflow obstruction.
• Fiberoptic endoscopy is most sensitive:
flexible rhino laryngoscopy.
Laryngeal Involvement in RA
• Intubation can lead to mucosal edema,
compromise of airway caliber and stridor and
airway obstruction post extubation.
• Risk Factors: Laxity of joint capsule and large
synovial folds.
Treatment
• Severe airway obstruction: Secure airways in
OR, Surgeon support, awake fiber optic
intubation.
• Helium/oxygen mixture improve airflow.
• Acute: systemic glucocorticoids, local
periarticular steroids can improve CA function.
• Chronic: surgery: lateralizing one of the vocal
folds, arytenoidectomy vs. tracheostomy.
Atlantoaxial instability
• C1-C2 instability causing brain stem or spinal
cord compression.
• Prevalence: 25%.
• Independent of disease duration or patient’s
age but is most common in patients with
severe peripheral joint involvement.
• Ligamentous laxity induced by inflammation.
Atlantoaxial instability
• High risk of neurologic injury for cervical
manipulation in RA patients.
• Avoiding hyperextension and maintaining
cervical spine in midline w/o extension.
• Awake fiberoptic intubation is recommended.
Wegener Granulomatosis
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Major upper airway life threatening complication.
Subglottic stenosis prevalence: 20%.
Acute inflammation or scar formation.
Corticosteroids, immunosuppression,
intralesional steroids.
• Tracheostomy.
• Intratracheal dilation injection ( intralesional
long acting corticosteroid injection and
mechanical dialtion).
Relapsing Polycondritis
• Recurrent episodes of inflammation of cartilaginous
and connective tissue structures.
• Type II collagenous antibodies.
• Respiratory involvement associated with high
mortality.
• Compromise of glottic, supra or subglottic, trachea
and first and second order bronchi.
Relapsing Polycondritis
• Encroachment of airway by inflammatory
swelling.
• Formation of mass of fibrous tissue.
• Dissolution of tracheobronchial with subsequent
collapse during respiration.
• Corticosteroids ( MTP ) and immunosuppression,
plasmapheresis.
• Surgery: tracheostomy in cases of subglottic
involvement.
• Endotracheal prostheses and stents.
Pulmonary Renal Syndromes in
ICU
Anti GBM Disease
• Acute Pulmonary hemorrhage, oliguric acute renal
failure and anti GBM antibodies.
• 1 case per 2 million white people.
Anti GBM Disease
• Type IV collagen.
• Alpha chains: alpha1 to 6.
• Alpha 3: lung, kidney, seminiferous duct, choroids
plexus, optic lens and inner ear.
• Autoimmune response to Alpha-3 NC-domain: Anti
GBM Syndrome.
• Genetic susceptibility: HL DR15, HLA DR 4
Pathogenesis
Anti GBM Disease
• Anti GBM antibodies ( anti alpha-3, Type IV
antibodies).
• Double positive: Anti GBM and ANCA p or
ANCA c.
• 20%-30% of Anti GBM are double positive,
>75% ANCA p positive.
• 8-10% ANCA vasculitis are double positive.
Anti GBM Disease
• Hemoptysis: severity is variable.
• Alveolar hemorrhage: infectious and non
infectious, cigarrete smoking.
• HLM in alveolar and small airways, interstitial
infiltrates, lymphocytic infiltration in alveolar
septae and peri broncovascular interstitium.
• DAD: proteinaceous infiltrates and hyaline
membranes.
Anti GBM Disease
• Crescent formation and GBM destruction.
• Epithelial crescents in more than 50% of the
glomeruli is a poor prognostic factor.
Therapy
• Pulse methylprednisolone, cyclophosphamide
and plasmapheresis.
• MP: 30mg/kg, on alternate days for 3 doses.
Follow by oral prednisone for 12 months.
• CP: 2mg/kg, daily dose, should be reduced by
0.5mg/kg every 3 months.
• Plasma exchange: 4 liter plasma exchanges
daily or on alternate days.
Small Vessel Vasculitis
• Wegener's: c-ANCA or PR3 ANCA (65%) or pANCA or MPO ANCA (20%).
• Microscopic Polyangiitis and CCS: p-ANCA or
MPO ANCA.
Treatment
• Accurate determination of disease severety.
• Remission induction phase.
• Maintenance phase.
Treatment
• Induction therapy: MP IV 7mg/kg on 3 consecutive
days, then prednisone 1mg/kg per day for 1 month,
alternate date schedule and the dose is reduced by
10mg/week on the second month.
• IV Cyclophosphamide: 0.5mg/kg at monthly intervals
( less side effects than oral)
• Oral Cyclophosphamide: 2mg/kg per day.
Treatment
• Rituximab (anti CD 20 chimeric monoclonal
antibody).
• Infliximab.
• Plasma exchange or plasmapheresis, twice daily for 7
days in patients with significant pulmonary
hemorrhage and renal failure.
• IVIG in severe pulmonary hemorrhage.
Catastrophic Antiphospholipid
Syndrome
• APLS: Thrombosis, thrombocytopenia,
recurrent fetal loss and increased APL
antibodies.
• CAPS: subset characterize with fulminant
clinical course with widespread vascular
occlusion involving at least three organs in
association with ACL or LA.
• Thrombocytopenia and MAHA.
Pathology and Pathophysiology
• Non inflammatory, thrombotic microangiopathy of
small vessels resulting in MOF.
• APL: immunoglobulins that bind plasma proteins or
phospholipid micro particles.
• Activation of platelets, monocytes, tumor cells or
endothelial cells leading to pro coagulant state.
Role of APL antibodies
• Tissue ischemia and necrosis leading to SIRS.
• SIRS= altered hemostasis, increased
coagulation and microvascular fibrin
deposition.
Catastrophic Antiphospholipid
Syndrome
• Prior history of APS in 50% to 70%.
• Precipitating factors are found in 22%.
• Infections, trauma, surgical procedures, tissue
biopsies, pregnancy and post fetal demise,
malignancy, withdrawal from anticoagulation.
Catastrophic Antiphospholipid
Syndrome
• Diffuse injury to the capillary endothelial and
epithelial cells resulting in ALI and ARDS.
• Microvascular thrombi causing endothelial
damage, neutrophil influx and cytokines
release.
• Alveolar hemorrhage .
Catastrophic Antiphospholipid
Syndrome
• Valvular vegetations.
• Coronary artery occlusion with cardiac failure
and circulatory collapse.
• Thrombus formation within the cardiac
chambers.
Catastrophic Antiphospholipid
Syndrome
• Renal thrombotic microangiopathy of the
glomerular capillaries and small renal
arteries.
Treatment
• Anticoagulation and r/o infection.
• Steroids, plasmapheresis, IVIG.
• Plasmaphresis: removal of B2GPI, cytokines
and mediators that promote coagulation.
SLE
SLE
• Infections is the most common form of
pulmonary involvement.
• Lupus Pneumonitis.
• Alveolar Hemorrhage.
• Acute Reversible Hypoxemia.
• Shrinking Lung Syndrome.
• Drug Reaction.
Acute Lupus Pneumonitis
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Exclusion diagnosis. Clinical diagnosis.
Dyspnea, cough, fever and hemoptysis.
R/O infection.
Incidence: 0.9-12%.
Initial presentation or in patients who have
been already diagnosed with SLE.
• Mortality: 50%
Acute Lupus Pneumonitis
• Inflammation and tissue injury, no vasculitis:
alveolitis, alveolar necrosis, alveolar
hemorrhage, edema, interstitial pneumonitis,
hyaline membranes, capillary thrombosis,
deposition of complement and
immunoglobulins.
Acute Lupus Pneumonitis
• High dose corticosteroids: 1-2 mg/day.
• Cyclophosphamide, Plasmapheresis.
DAH
• Mortality 40%-90%.
• 2% of SLE patients.
• Young woman with new or establish diagnosis
of SLE.
• Cough, dyspnea, fever, hemoptysis, fall in
hematocrit (70%-100%) and pulmonary
infiltrates.
• Elevated ANA and low complement levels.
• Active Nephritis.
DAH
• BAL: Increasingly or persistently bloody
returns.
• Mononuclear and polymorphonuclear cell
infiltrates, hyaline membranes, alveolar
necrosis, edema, microvascular thrombosis,
hemosiderin laden macrophages and
capillaritis.
DAH
• High dose corticosteroids ( prednisone 1-3
mg/kg/day or MTP 1g/day for 3 days followed by
prednisone 60mg/day).
• Adjunctive immunosuppressive ( Cyclophosphamide
500-1000mg/m2/day every 4 weeks) and
plasmapheresis ( three to four sessions) in critically ill
or non responders.
• Broad spectrum antibiotics.
• In patients on MV, antibiotics were continued until
extubation.
Drug Reaction
• Cellular interstitial pneumonia: azathioprine,
mycophenolate mofetil.
• Chronic eosinophilic pneumonia: NSAIDS.
• Early onset pneumonitis or upper lobe
predominance fibrosis and bilateral pleural
thickening: Cyclophosphamide.
• MTX induced lung injury.
Shrinking Lung Syndrome
• Dyspnea, respiratory muscle dysfunction,
small lung volume, elevated hemi diaphragms,
basilar atelectasis.
• Respiratory muscle weakness, including
diaphragmatic dysfunction.
• Steroids.
Acute Reversible Hypoxemia
• Active SLE and acute onset of hypoxemia with
normal radiologic imaging studies.
• Endothelial cell and complement-activated
neutrophil aggregation within pulmonary
capillaries (Pulmonary leuko-aggregation).
• Elevated A-a gradient, reduced VC and DLCO.
• Elevated complement degradation products.
• Steroids.
Neuropsychiatric Manifestations
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CVA
Transverse Myelitis
Seizures
Aseptic Meningitis
CVA
• RR for stroke: 8.
• 5%-20%.
• Association with APL antibodies, anti neuronal
antibodies, and emboli from cardiac valvular
lesions.
Transverse Myelitis
• Infrequent manifestation. 1%-2%.
• Early manifestation or within 5 years of diagnosis.
• Vasculitis or arterial thrombosis associated with
APL antibodies.
• CSF: elevated proteins, pleocytosis, low glucose
(<30mg/dl)
• MRI: Cord edema.
• Prednisone, Cyclophosphamide and
Plasmapheresis.
Seizures
• Common manifestation.
• Grand mal seizures are most common.
• Multifactorial: anti neuronal antibodies, focal
ischemia, infarcts caused by vasculitis or APL
antibodies, embolic phenomenon and
hemorrhage.
Aseptic Meningitis
• Headache, meningeal signs and CSF
pleocytosis (<200-300 cells, lymphocytes).
• Respond to corticosteroids.
• Rule out infectious process, NSAIDS or
Azathioprine induced aseptic meningitis.
Renal Failure
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Drugs: NSAIDs
Hypovolemia
Sepsis
Previous renal disease.
Lupus Nephritis: urinary sediment:
proteinuria, casts, RBC.
• Low complement levels and elevation of anti
DNA antibody.
SLE/Renal Failure
• Before to start aggressive
immunosuppression, considerer degree of
disease reversibility.
• Disease reversibility: Renal biopsy?.
Scleroderma
• Limited cutaneous sclerosis (CREST): Raynaud
phenomenon and skin thickening in face and
distal extremities.
• PAH.
• Diffuse systemic sclerosis: aggressive course,
constitutional symptoms, widespread skin
thickening, gastrointestinal involvement,
pulmonary fibrosis or renal disease.
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PAH
Acute Aspiration
Alveolar Hemorrhage
Renal Crisis
PAH
• Prevalence of PAH is 10-15%.
• CREST: isolated phenomenon, absence of
pulmonary fibrosis.
• Diffuse Scleroderma: advanced pulmonary
fibrosis.
• PAH symptoms can predate SSc
manifestations.
• More prevalent in patients with limited
cutaneous sclerosis.
PAH
• Autoimmune process causing damage of vascular
endothelium.
• Transforming Growth Factor Beta and fibroblast
proliferation.
• Infiltration of mononuclear cells, Th2 lymphocytes.
• High prevalence of anti endothelial cell antibodies
(AECA).
• IgM AECA has been associated with increase production
of endotelin 1.
• Decreased NO and Prostacyclin.
• Increased Thromboxane and endotelin 1.
Right Ventricular Failure
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R/O other causes of RVF:
Infectious process
PE
Ischemic cardiomyopathy
Pericardial tamponade
Right Ventricular Failure
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Oxygen
Diuretics
Vasodilators
Inotropes
Right Ventricular Failure
• Inhale NO: less risk for systemic hypotension
with significant decrease in PVR, mPAP, RVEDP
and increases CO.
• PGE1: systemic hypotension, mainly in
patients with poor vasoreactivity, low CO or
high RAP.
Right Ventricular Failure
• Dobutamine,amrinone,milrinone,
dopexamine: inotropic vasodilators.
• NE rise SBP, does not significantly rise PVR and
excellent inotrope.
• Pulmonary vasodilators + systemic
vasoconstricting inotropes
• Atrial septostomy?
Pulmonary Renal Syndrome
• Rare complication associated with mortality.
• Exclusion diagnosis: DAH + ARF.
• More than 80% of patients has normal BP vs.
hypertensive crises in SSc renal crisis.
• Associated with MAHA and thrombocytopenia.
• Segmental necrotizing crescentic glomerulonephritis.
• Plasma renin activity.
• Poor response to therapy.
Hypertensive Renal Crisis
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Acute malignant hypertension.
Diffuse cutaneous disease.
High dose corticosteroids.
High renin states.
Large doses of ACEI.
ARB, CCB, prostacyclin, ERA in refractory
cases.
Pathogenesis
• Endothelial cell injury, intimal proliferation
with luminal narrowing, decreased renal
perfusion, increased renin production,
malignant hypertension and RF.
• ET-1
Treatment
• ACEi
• HD
Bibliography
Bibliography
• Alveolar Hemorrhage in SLE: Presentation and
Management. Chest 2000;118;1083-1090.
• Pulmonary and Thrombotic Manifestations of
SLE. Chest 2008;133;271-280.
• Pulmonary Renal Syndromes in the ICU. Crit
Care Clin.2002 (18):881-895.
• CAPS. Crit Care Clin.2002(18):805-817.